Biological Activity and Use of Boron Compounds
Boron compounds are known to show a variety of different biological activities. Very often, boron compounds snow enzyme inhibitory activity, including inhibition of a number of enzymes. These functions have been demonstrated alone, and in combination with various co-inhibitors. For example, borates have been demonstrated to inhibit L-amino acid oxidase in a mixture with butanediol, by interacting with the arginine residue in the active site. (Christman M F, Cardenas J M: Experientia 38(5): 537-538 (1982)).
Borates and butanediol are also known to inhibit citrate/isocitrate-hydro-lyase, EC 4.2.1.3, again by interacting with the arginine residue from the active site. (Gawron O, Jones L: Biochem Biophys Acta 484 (2): 453-464 (1977)). Also, 2,3-butanediol or 1,2-cyclohexanedione in the presence of borates interacts specifically with the guanidino group from arginine, and this fact was used for determination of arginine residues in the active site of the examined enzymes. In this way Dietl, T. and Tschesche, H. (Hoppe Seylers Z Physiol Chem: 357(5): 657-665 (1976)) proved arginine residue is present in the active site of proteinases.
As yet another example, borates (at low concentrations) are known to inhibit glyceraldehyde-3-phophate dehydrogenase from human, pig and rabbit muscle. However, in greater concentration (above 6 mM) borates inhibit esterase and acetylphosphatase activities. (Wolny M: Eur J Biochem 80 (2): 551-556 (1977)).
An interesting biological activity of borates was noticed in the case of palytoxin induction of the histamine release from rat mast cells. In the presence of borates the activity of palytoxin was increased ten times (Chatwal G S, Ahnert-Hilger G, Beress I, Habermann E: Int Arch Allergy Appl Immunol 68 (2): 97-100 (1982)).
Borates inhibit methylation of catechol estrogen and pyrocatechol by catechol-O-methyltransferase (Beattie J H, Weersink E: J Inorg Biochem 46 (3): 153-160 (1992)).
Several naturally occurring antibiotics contain boron as an essential structural element, such as boromycin, an anti-HIV antibiotic (Kohno J, et al: Biosci Biotechnol Biochem (Japan) 60 (6), 1036-7 1996)), or tetralons, new boron-containing antibiotics from a Myxobacterium, Sporangium cellulosum (Irschik H, Schummer D, Gerth K, Hofle G, Reichenbach H: J Antibiot (Tokyo) (Japan) 48 (1): 26-30 (1995)).
Borates are experimentally used in surgery as agents which promote healing of open wounds (Humzah M D, Marshall J, Breach N M: J R Coll Surg Edinb (England) 41(4): 269-70 1996); McCowan M, Aikten F: J Wound Care (England) 6(5): 248-249 (1997); Bliss M R: J Wound Care (England) 6(5): 248-249 (1997)).
Larvicidal effects of ingestion of boric acid and disodium octaborate tetrahydrate by cat fleas was recently described by Hinkle N C., Koehler P G, and Patterson R S in J Med Entomol (United States) 32(4): 424-7 (1995).
Some specific organoboron compounds (such as cyanotriphenylborate) were shown to be subtype-specific blockers of glycine receptor chloride channels (Rundstrom N, Schmidien V, Betz H, Bormann J, Langosch D: Proc Acad Sci U S A (United States) 91(19): 8950-4 (1994)).
Treatment of chick embryo pelvic cartilage with 1-3% aqueous boric acid induces release of proteoglycans, collagen and TNF-alpha into the culture medium, but at the same time strongly decreases their intracellular synthesis. However, the same concentration of boric acid, in the presence of great molar excess of glucose in culture medium, does not decrease intracellular protein synthesis, but still stimulates protein secretion into the culture medium (Benderdour M, Hess K, Dzondo-Gadet M, Dousset B: Biochem Biophys Res Commun 234 (1): 263-8 (1997).
It has been proposed that borons interact actively with Ca-metabolism, but exact mechanisms of this interaction have not yet been determined (Nielsen F, Muller L, Gallagher S: J Tace Elem Exp Med 3: 45-54 (1990). Specific biological Ca--B interaction was also described by T. Maruyama et al (J Biochem (Tokyo) 122(3): 498-505 (1997)), who showed that 2-amonoethoxydiphenyl borate (2-APB) inhibited Ins (1,4,5)P3-induced Ca release from rat cerebral microsomal preparations. Addition of 2-APB to the extracellular environment inhibited the cytosolic Ca rise in intact cells such as human platelets and neutrophiles stimulated by thrombin or leukotriene B4 LTB4).